Are Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs) indicated for Hypertension (HTN) in Chronic Kidney Disease (CKD) patients on Hemodialysis?

ACE Inhibitors and ARBs in Hemodialysis Patients with Hypertension

ACE inhibitors or ARBs are reasonable second-line antihypertensive options for CKD patients on hemodialysis, but beta-blockers and calcium channel blockers should be prioritized as first-line therapy, with volume management through ultrafiltration and sodium restriction as the cornerstone of treatment. 1, 2

Primary Treatment Approach: Volume Management First

Before initiating or escalating any antihypertensive medication, achieve dry weight through adequate ultrafiltration and enforce dietary sodium restriction, as volume overload underlies most hypertension in dialysis patients. 1, 2, 3 Target predialysis blood pressure should be 140/90 mmHg measured in the sitting position. 1, 2

First-Line Pharmacologic Options

Beta-Blockers

• Beta-blockers demonstrate the strongest mortality benefit in dialysis patients and should be preferred for patients with previous myocardial infarction or established coronary artery disease. 1, 3
• Carvedilol reduced cardiovascular death versus placebo in hemodialysis patients with dilated cardiomyopathy. 3
• Atenolol showed fewer heart failure hospitalizations compared to ACE inhibitors in hypertensive hemodialysis patients with left ventricular hypertrophy. 3

Calcium Channel Blockers

• Amlodipine reduced cardiovascular events compared with placebo in hemodialysis patients with hypertension in randomized controlled trials. 1, 3
• Calcium channel blockers are associated with decreased total and cardiovascular mortality in observational studies. 1, 3
• Amlodipine is preferred when patients lack specific cardiovascular indications for beta-blockers. 3

Second-Line Role of ACE Inhibitors/ARBs

Potential Benefits

• ACE inhibitors/ARBs may reduce left ventricular mass index according to meta-analyses. 1, 2, 3
• These agents may preserve residual kidney function, which is particularly important in peritoneal dialysis patients. 1, 2, 3
• ACE inhibitors have been associated with decreased mortality in observational studies of ESRD patients. 2, 4

Important Limitations

• Fosinopril did not reduce cardiovascular events or death compared to placebo in hemodialysis patients with left ventricular hypertrophy, showing inconsistent cardiovascular outcome benefits compared to the robust evidence in pre-dialysis CKD. 3
• The strong evidence supporting ACE inhibitors/ARBs as first-line therapy applies specifically to CKD patients NOT on dialysis with albuminuria. 5
• Guidelines for pre-dialysis CKD patients recommend ACE inhibitors/ARBs as first-line for those with albuminuria ≥300 mg/24h, but these recommendations do not extend to dialysis patients. 5

Treatment Algorithm for Hemodialysis Patients

1. Optimize volume status through ultrafiltration and sodium restriction (target predialysis BP 140/90 mmHg). 1, 2, 3

2. If coronary artery disease or heart failure present: Start with beta-blockers (preferably nondialyzable agents like propranolol if no intradialytic hypotension). 1, 2, 3

3. If no specific cardiovascular indications: Start with calcium channel blockers (amlodipine preferred). 1, 3

4. If blood pressure remains uncontrolled: Add ACE inhibitor/ARB as second agent, particularly if residual kidney function exists. 1, 2, 3

5. If BP remains >140/90 mmHg despite achieving dry weight and using three appropriate agents: Evaluate for secondary causes of resistant hypertension. 2

Critical Safety Considerations

Hyperkalemia Risk

• ACE inhibitors and ARBs increase risk of hyperkalemia, especially in dialysis patients. 5, 6, 7, 8
• The incidence of hyperkalemia with ACE inhibitors/ARBs in CAPD patients was 13%, with most events occurring in patients with inadequate dialysis (Kt/V <2) or low peritoneal transport status. 9
• Monitor serum potassium frequently when using these agents. 6, 7, 8

Dual RAAS Blockade

• Combination of ACE inhibitors with ARBs should be avoided due to increased risks of hyperkalemia and acute kidney injury without additional benefit. 5, 6, 7
• The VA NEPHRON-D trial demonstrated that combining losartan with lisinopril increased hyperkalemia and acute kidney injury without additional benefit. 7

Dialyzability Considerations

• Hemodialysis reduces blood levels of some ACE inhibitors (enalapril, ramipril) but not others (benazepril, fosinopril). 2
• ARB levels do not change significantly during dialysis. 2
• Consider medication timing to minimize intradialytic hypotension—preferentially administer at night to control nocturnal BP. 3

Common Pitfalls to Avoid

• Never initiate or escalate antihypertensives without first assessing volume status, as most dialysis hypertension is volume-mediated. 1, 2, 3
• Do not overlook residual kidney function preservation when selecting agents—ACE inhibitors/ARBs offer this specific benefit. 1, 2, 3
• Avoid ACE inhibitors in patients treated with polyacrylonitrile dialysis membranes due to risk of anaphylactoid reactions. 2
• Check for postural hypotension regularly when treating with any BP-lowering drugs. 5, 3
• Avoid highly dialyzable beta-blockers (atenolol, metoprolol) if intradialytic arrhythmia protection is needed. 3